在Ser-Thr激酶中基激活的古代起源
Adelajda Hadzipasic1,2, Christopher Wilson1,2, Vy Nguyen1,2
1Department of Biochemistry, Brandeis University, Waltham, MA 02454, USA.
概括
研究了Aurora A激酶及其激活剂TPX2 (Xklp2的向蛋白) 的异质调节的演变. 古老的自化机制保持稳定,而TPX2介导的调节则在激酶本身中演变.
科学领域:
- 生物化学
- 进化生物学
- 分子生物学
背景情况:
- 对于许多细胞过程而言,体调节至关重要.
- 了解菌的演变为我们提供了对生物机制的基本见解.
研究的目的:
- 重建和实验分析Aurora A激酶和TPX2之间的异质激活的演化轨迹.
- 研究激酶调节的古代起源和随后的发展.
主要方法:
- 复制祖先的序列来复活祖先的蛋白质.
- 对复活的祖先激酶和激活剂的实验性表征.
- 蛋白与蛋白相互作用和调节机制的分析.
主要成果:
- 最古老的激活机制,激活循环的自化,是古老的和高度保存的 (>10亿年).
- 在TPX2出现后,Aurora A激酶与微管相关蛋白TPX2之间发生了有效的结合.
- 基因酶的TPX2介导的基调节逐渐演变,基因基因位于基因酶内,而不是主要通过同进化.
结论:
- 这种调节有着古老的根源,
- 特定的全调节的演变,如TPX2的Aurora A激酶,可以在调节的蛋白质本身中编码.
- 这项研究阐明了一种全性调节的新型进化途径,强调了酶的内在适应能力.
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